Porphyromonas gingivalis

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Porphyromonas gingivalis
Scientific classification OOjs UI icon edit-ltr.svg
Domain: Bacteria
Phylum: Bacteroidota
Class: Bacteroidia
Order: Bacteroidales
Family: Porphyromonadaceae
Genus: Porphyromonas
Species:
P. gingivalis
Binomial name
Porphyromonas gingivalis
(Coykendall et al. 1980) Shah and Collins 1988

Porphyromonas gingivalis belongs to the phylum Bacteroidota and is a nonmotile, Gram-negative, rod-shaped, anaerobic, pathogenic bacterium. It forms black colonies on blood agar.

Contents

It is found in the oral cavity, where it is implicated in periodontal disease, [1] as well as in the upper gastrointestinal tract, the respiratory tract, and the colon. It has been isolated from women with bacterial vaginosis. [2]

Collagen degradation observed in chronic periodontal disease results in part from the collagenase enzymes of this species. It has been shown in an in vitro study that P. gingivalis can invade human gingival fibroblasts and can survive in the presence of antibiotics. [3] P. gingivalis invades gingival epithelial cells in high numbers, in which case both bacteria and epithelial cells survive for extended periods of time. High levels of specific antibodies can be detected in patients harboring P. gingivalis.

P. gingivalis infection has been linked to Alzheimer's disease [4] and rheumatoid arthritis. It contains the enzyme peptidyl-arginine deiminase, which is involved in citrullination. [5] Patients with rheumatoid arthritis have increased incidence of periodontal disease; [6] antibodies against the bacterium are significantly more common in these patients. [7]

P. gingivalis is divided into K-serotypes based upon capsular antigenicity of the various types. [8] These serotypes have been the drivers of observations regarding bacterial cell to cell interactions to the associated serotype-dependent immune response and risk with pancreatic cancer. [9] [10]

Genome

The genome of P. gingivalis was described in 2003 revealing 1,990 open reading frames (i.e. protein-coding sequences), encoded by 2,343,479 bp, with an average G+C content of 48.3%. [11] An estimated 463 genes are essential. [12]

Virulence factors

Gingipain

Arg-gingipain (Rgp) and lys-gingipain (Kgp) are endopeptidase enzymes secreted by P. gingivalis. These gingipains serve many functions for the organism, contributing to its survival and virulence. [13]

Arg-gingipains have been found to play a key role in the collection of nutrients for P. gingivalis survival. Rgp degrades large peptides of the host organism to provide the bacterium with an abundant nitrogen and carbon source from human serum albumin. [14] P. gingivalis can also degrade transferrin within host cells which provides the organism with an abundant iron source needed to perform multiple cellular functions. [15]

The gingipains are also responsible for a number of necessary functions related to host invasion and colonization. Rgp gingipains are necessary for adhesion and invasion as they processed precursor proteins of long fimbriae. [15] The P. gingivalis genes encoding RgpA, Kgp, and hemagglutinin A (HagA) were strongly expressed after incubation with T. denticola. The hemagglutinin adhesion domain-containing proteins act to increase adhesive capacities of P. gingivalis with other bacterial species. [16] They are also associated with coordinating the integrity of the biofilm in the developing and maturation phase. [17] Lys- gingipains (Kgp) can bind to immobilized matrix proteins fibrinogen and fibronectin and may have a role in host colonization. [18]

Gingipains also have the ability to degrade multiple signals of the host immune response. They have the ability to cleave subclass 1 and 3 IgG antibodies [19] as well as proinflammatory cytokines such as IL-1β, IL-2, IL-6, TNF-α and IL-8 in regions of high P. gingivalis concentration, [20] impairing host immune response function. Rgp can inhibit IL-2 accumulation in T-cells, which enables it to evade the host adaptive immune response, by modulating T-cell communication and proliferation. [21]

Gingipains are key factors in tissue damage symptoms of periodontitis, which results from the degradation of matrix metalloproteins, collagen, and fibronectin. [15] Degradation of these substrates interferes with interactions between host cells and the extracellular matrix, therefore impeding wound healing and causing destruction of periodontal tissues. [15] Rgp is responsible for eliciting the host inflammatory response via the p38α MAPK transduction pathway. This response likely contributes to the inflammatory nature of periodontitis and is involved in tissue and bone destruction. [14]

Gingipains have been associated with Alzheimer's disease (AD). Gingipains were discovered from TMAs of patients exhibiting AD brain pathology. Both RgpB and Kgp were discovered from hippocampus and cerebral cortex of AD patients and were found to be associated with tau load, a marker for AD pathology and ubiquitin, which accumulates in tau tangles and amyloid beta plaques in AD brain. P. gingivalis 16S rRNA was also discovered in the cerebral cortex and csf of AD brains. Pretreatment with gingipain inhibitors protected neuron cell degradation caused by administration of gingipains in murine model. [4]

Capsular polysaccharide

The encapsulated strain of P. gingivalis is much more virulent than the nonencapsulated strain in a mouse abscess model. [22] The capsule is a capsular polysaccharide and when present down regulates cytokine production especially proinflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α, indicating host evasion responses. [20] [22] However, other studies have found the capsular polysaccharide to elicit host immune responses like neutrophil migration and dose and time dependent expression of cell migration chemokines like MCP-1, KC, MIP-2 and RANTES in capsular polysaccharide-challenged murine peritoneal macrophages. These conditions are likely to contribute to the inflammatory lesions observed in periodontitis. [23]

Vaccines made from capsular polysaccharide of P. gingivalis apparently impair oral bone loss in murine models. These vaccines have been able to elicit potent immune responses such as increased IgM and IgG responses that recognize whole P. gingivalis organisms. [24]

Fimbriae

Fimbriae are appendages involved in cellular attachment and greatly contribute to virulence and are found on many Gram-negative and some Gram-positive bacteria.[ citation needed ]

P. gingivalis virulence is heavily associated with fimbriae as they have been characterized to be key factors in adhesion, invasion, and colonization. Fimbriae are also responsible for invasion of membrane vesicles into host cells. [15] They were found to bind to cellular α5β1 integrins, which mediated adherence and impaired the homeostatic controls of host cells. [25] Fimbriae were also found to be associated with modulating β2 integrin adhesive activity for uptake by monocytes using the CD14/TLR2/PI3K signaling complex, which may contribute to intracellular evasion tactics by P. gingivalis. [26] P. gingivalis has long fimbriae, short fimbriae, and accessory components, each of which have distinct functions. [17]

Long fimbriae

Long fimbriae (FimA), also known as major fimbriae, are long, peritrichous, filamentous components. [27] They have a role in initial attachment and organization of biofilms, as they act as adhesins that mediate invasion and colonization of host cells contributing to P. gingivalis virulence. [17]

Short fimbriae

Short fimbriae (Mfa1), also known as minor fimbriae, have distinct roles from long fimbriae and are characterized to be essential for cell-cell auto aggregation and recruitment for microcolony formation. [27] Short fimbriae are involved in cell-cell adhesion with other dental commensals. It was found to coadhere and develop biofilm in conjunction with Streptococcus gordonii by interaction with SspB streptococcal surface polypeptide. [28] This interaction may be essential in the invasion of dentinal tubules by P. gingivalis. [29]

Accessory fimbriae

Fim C, D, and E accessory components associate with the main FimA protein and have a role in binding with matrix proteins and interaction with CXC-chemokine receptor 4. Loss of function experiments have confirmed that P. gingivalis mutants deficient for Fim C, D, or E have drastically attenuated virulence. [30]

Evasion of host defenses and immune responses

P. gingivalis has many ways of evading host immune responses which affects its virulence. It does this by using a combination of gingipain proteases, a capsular polysaccharide, induction of host cell proliferation, and the cleavage of chemokines responsible for neutrophil recruitment. [19] [31]

Virulent P. gingivalis further modulates leukocyte recruitment by proteolysis of cytokines and chemokines that are secreted by the host cells. The arg-gingipain and lys-gingipains are responsible for this proteolysis. In a study using a mouse model, P. gingivalis was specifically found to down-regulate IL-8 induction, causing delayed neutrophil recruitment. Prevention of neutrophil recruitment may inhibit the clearance of the bacterium from the site of infection allowing for colonization. [31] P. gingivalis is able to evade opsonophagocytosis from granulocytes by using Gingipain K (Kgp) to cleave IgG 1 and 3. This further modulates immune response by impairing signaling. [19] Other studies have found that P. gingivalis can subvert the complement pathway through C5αR and C3αR, which modulates the killing capacity of leukocytes, allowing for uncontrolled bacterial growth. [31] [32] [33] P. gingivalis was also found to inhibit pro inflammatory and antimicrobial responses in human monocytes and mouse macrophages by fimbrial binding to CXCR4, inducing PKA signaling and inhibiting TLR-2-mediated immune response. [34]

Once in the host cells, P. gingivalis is capable of inhibiting apoptosis by modulating the JAK/Stat pathway that controls mitochondrial apoptotic pathways. [35] [17] A proliferative phenotype may be beneficial to the bacterium as it provides nutrients, impairs host cell signaling, and compromises the integrity of the epithelial cell layer, allowing for invasion and colonization. [17]

Ecology

P. gingivalis plays an important role in the onset of chronic adult periodontitis. [36] Though it is found in low abundance in the oral cavity, it causes a microbial shift of the oral cavity, allowing for uncontrolled growth of the commensal microbial community. This leads to periodontitis through the disruption of the host tissue homeostasis and adaptive immune response. [37] After using laser capture microdissection plus qRT-PCR to detect P. gingivalis in human biopsies, colocalization of P. gingivalis with CD4+ T cells was observed. [38] However, the infection mechanism of T cells by P. gingivalis remains unknown.[ citation needed ]

P. gingivalis has been associated with increasing the virulence of other commensal bacteria in both in vivo and in vitro experiments. P. gingivalis outer membrane vesicles were found to be necessary for the invasion of epithelial cells of Tannerella forsythia . [39] P. gingivalis short fimbriae were found to be necessary for coculture biofilm formation with Streptococcus gordonii . [28] Interproximal and horizontal alveolar bone loss in mouse models are seen in coinfections involving P. gingivalis and Treponema denticola . [40] The role of P. gingivalis in periodontitis is studied using specific pathogen-free mouse models of periodontal infections. In these models, P. gingivalis inoculation causes significant bone loss, which is a significant characteristic of the disease. In contrast, germ free mice inoculated with a P. gingivalis monoinfection incur no bone loss, indicating that P. gingivalis alone cannot induce periodontitis. [31]

Pathogenesis and Cardiovascular Comorbidities

While P. gingivalis is a part of the typical microbiotic ecosystem of the oral cavity in humans, it can also become pathogenic is provided with sufficient opportunity. When this occurs, the resultant infection is known as gingivitis or periodontitis.

Periodontal disease, which an infection of the gum tissue driven primarily by P. gingivalis, has been theorized to be linked with other systemic diseases, including Alzheimer’s, atherosclerosis and other cardiovascular diseases. Though there exists no scientific consensus on the mechanism by which these disease processes are linked, evidence for the connection between periodontal disease and cardiovascular diseases including atherosclerosis has been found in both statistical study of human populations, [41] and in vivo studies using a mouse model. [42]

It is thought that periodontitis is linked to cardiovascular disease due to inflammation pathways, which the two pathologies have in common. The inflammation pathway of periodontitis is such that as the infection grows, bacteria, including P. gingivalis are targeted by neutrophils and natural killer immune cells. These cells phagocytize the bacteria, while simultaneously cytokine molecules in the area lead to a proinflammatory environment. This proinflammatory environment is also rich in intercellular signaling molecules including tumor necrosis factor-alpha, interleukins (interleukin 1, interleukin 4, interleukin 10), interferons and transforming growth factor beta. These molecules recruit more enzymes and transcription factors, which then in turn recruit more immune cells, forming a positive feedback loop which can make the immune response, and therefore the inflammation become chronic and systemic. Chronic inflammation of gum tissue can lead to a loss of this tissue and of bone tissue as well. The inflammation upregulates production of RANKL, an intercellular signaling molecule that promotes bone tissue dissolution, leading to a gradual loss of bony tissue. P. gingivalis infection is also thought to lead to oxidative stress. Both chronic systemic inflammation and oxidative stress are factors associated with the onset of cardiovascular disease, and are proposed mechanisms by which periodontal disease may, if it indeed is causationally linked to cardiovascular disease, accelerate the disease process of a cardiovascular disease. [43]

While invasive P. gingivalis is associated with various forms of cardiovascular disease, including stroke, coronary artery disease, atrial fibrillation, and heart failure, the best evidence of a direct causational link is between invasive P. gingivalis (periodontal disease) and atherosclerosis. In vivo and in vitro animal models have found that the fimbriae of P. gingivalis promote host cell entry and atherothrombotic lesion formation once the bacteria enter the bloodstream, such as through lesions in the mouth. P. gingivalis has been shown to accelerate the atherosclerosis disease pathway in mice, as well as being found in human atherosclerotic plaque lesions. [44]

See also

Related Research Articles

<span class="mw-page-title-main">Periodontal disease</span> Medical condition

Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main cause of tooth loss for adults worldwide. In its more serious form, called periodontitis, the gums can pull away from the tooth, bone can be lost, and the teeth may loosen or fall out. Halitosis may also occur.

<i>Streptococcus pneumoniae</i> Species of bacterium

Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, spherical bacteria, alpha-hemolytic member of the genus Streptococcus. They are usually found in pairs (diplococci) and do not form spores and are non motile. As a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies.

<span class="mw-page-title-main">Bacterial capsule</span> Polysaccharide layer that lies outside the cell envelope in many bacteria

The bacterial capsule is a large structure common to many bacteria. It is a polysaccharide layer that lies outside the cell envelope, and is thus deemed part of the outer envelope of a bacterial cell. It is a well-organized layer, not easily washed off, and it can be the cause of various diseases.

<i>Aspergillus fumigatus</i> Species of fungus

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Dental plaque is a biofilm of microorganisms that grows on surfaces within the mouth. It is a sticky colorless deposit at first, but when it forms tartar, it is often brown or pale yellow. It is commonly found between the teeth, on the front of teeth, behind teeth, on chewing surfaces, along the gumline (supragingival), or below the gumline cervical margins (subgingival). Dental plaque is also known as microbial plaque, oral biofilm, dental biofilm, dental plaque biofilm or bacterial plaque biofilm. Bacterial plaque is one of the major causes for dental decay and gum disease.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces, usually in the host they are infecting or living in. Adhesins are a type of virulence factor.

Aggregatibacter actinomycetemcomitans is a Gram-negative, facultative anaerobe, nonmotile bacterium that is often found in association with localized aggressive periodontitis, a severe infection of the periodontium. It is also suspected to be involved in chronic periodontitis. Less frequently, A. actinomycetemcomitans is associated with nonoral infections such as endocarditis. Its role in aggressive periodontitis was first discovered by Danish-born periodontist Jørgen Slots, a professor of dentistry and microbiology at the University of Southern California School of Dentistry.

Treponema denticola is a Gram-negative, obligate anaerobic, motile and highly proteolytic spirochete bacterium. It is one of four species of oral spirochetes to be reliably cultured, the others being Treponema pectinovorum, Treponema socranskii and Treponema vincentii. T. denticola dwells in a complex and diverse microbial community within the oral cavity and is highly specialized to survive in this environment. T. denticola is associated with the incidence and severity of human periodontal disease. Treponema denticola is one of three bacteria that form the Red Complex, the other two being Porphyromonas gingivalis and Tannerella forsythia. Together they form the major virulent pathogens that cause chronic periodontitis. Having elevated T. denticola levels in the mouth is considered one of the main etiological agents of periodontitis. T. denticola is related to the syphilis-causing obligate human pathogen, Treponema pallidum subsp. pallidum. It has also been isolated from women with bacterial vaginosis.

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Porphyromonas is a Gram-negative, non-spore-forming, obligately anaerobic and non-motile genus from the family Porphyromonadaceae. There were 16 different Porphyromonas species documented as of 2015, which reside in both animal and human reservoirs. It was discovered more recently that Porphyromonas also exist in the environment, albeit to a lesser extent. This genus is notably implicated in the modulation of oral cavity, respiratory tract, and gastrointestinal tract disease states. It is suggested that Porphyromonas either operate as benign bacteria pertinent to host immunity or are potential pathobionts that opportunistically provoke diseased states when homeostasis is disrupted. Despite its characterization not being fully elucidated due to sparse research, various studies report the prevalence of this genus at 58.7% in healthy states compared with 41.3% in diseased states.

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Gingipain K is an enzyme. This enzyme catalyses the following chemical reaction

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References

  1. ↑ Naito M, Hirakawa H, Yamashita A, Ohara N, Shoji M, Yukitake H, et al. (August 2008). "Determination of the genome sequence of Porphyromonas gingivalis strain ATCC 33277 and genomic comparison with strain W83 revealed extensive genome rearrangements in P. gingivalis". DNA Research. 15 (4): 215–25. doi:10.1093/dnares/dsn013. PMC   2575886 . PMID   18524787.
  2. ↑ Africa CW, Nel J, Stemmet M (July 2014). "Anaerobes and bacterial vaginosis in pregnancy: virulence factors contributing to vaginal colonisation". International Journal of Environmental Research and Public Health. 11 (7): 6979–7000. doi: 10.3390/ijerph110706979 . PMC   4113856 . PMID   25014248.
  3. ↑ Irshad M, van der Reijden WA, Crielaard W, Laine ML (December 2012). "In vitro invasion and survival of Porphyromonas gingivalis in gingival fibroblasts; role of the capsule". Archivum Immunologiae et Therapiae Experimentalis. 60 (6): 469–76. doi:10.1007/s00005-012-0196-8. PMID   22949096. S2CID   14254746.
  4. 1 2 Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. (January 2019). "Porphyromonas gingivalis in Alzheimer's disease brains: Evidence for disease causation and treatment with small-molecule inhibitors". Science Advances. 5 (1): eaau3333. Bibcode:2019SciA....5.3333D. doi:10.1126/sciadv.aau3333. PMC   6357742 . PMID   30746447.
  5. ↑ Wegner N, Wait R, Sroka A, Eick S, Nguyen KA, Lundberg K, et al. (September 2010). "Peptidylarginine deiminase from Porphyromonas gingivalis citrullinates human fibrinogen and α-enolase: implications for autoimmunity in rheumatoid arthritis". Arthritis and Rheumatism. 62 (9): 2662–72. doi:10.1002/art.27552. PMC   2941529 . PMID   20506214.
  6. ↑ Berthelot JM, Le Goff B (December 2010). "Rheumatoid arthritis and periodontal disease". Joint Bone Spine. 77 (6): 537–41. doi:10.1016/j.jbspin.2010.04.015. PMID   20646949.
  7. ↑ Ogrendik M, Kokino S, Ozdemir F, Bird PS, Hamlet S (June 2005). "Serum antibodies to oral anaerobic bacteria in patients with rheumatoid arthritis". MedGenMed. 7 (2): 2. PMC   1681585 . PMID   16369381.
  8. ↑ American Academy of Periodontology 2010 In-Service Exam, question A-85
  9. ↑ Michaud DS, Izard J, Wilhelm-Benartzi CS, You DH, Grote VA, Tjønneland A, et al. (December 2013). "Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study". Gut. 62 (12): 1764–70. doi:10.1136/gutjnl-2012-303006. PMC   3815505 . PMID   22990306.
  10. ↑ Rosen G, Sela MN (March 2006). "Coaggregation of Porphyromonas gingivalis and Fusobacterium nucleatum PK 1594 is mediated by capsular polysaccharide and lipopolysaccharide". FEMS Microbiology Letters. 256 (2): 304–10. doi: 10.1111/j.1574-6968.2006.00131.x . PMID   16499621.
  11. ↑ Nelson KE, Fleischmann RD, DeBoy RT, Paulsen IT, Fouts DE, Eisen JA, et al. (September 2003). "Complete genome sequence of the oral pathogenic Bacterium porphyromonas gingivalis strain W83". Journal of Bacteriology. 185 (18): 5591–601. doi:10.1128/jb.185.18.5591-5601.2003. PMC   193775 . PMID   12949112.
  12. ↑ Hutcherson JA, Gogeneni H, Yoder-Himes D, Hendrickson EL, Hackett M, Whiteley M, et al. (August 2016). "Comparison of inherently essential genes of Porphyromonas gingivalis identified in two transposon-sequencing libraries". Molecular Oral Microbiology. 31 (4): 354–64. doi:10.1111/omi.12135. PMC   4788587 . PMID   26358096.
  13. ↑ Sheets SM, Robles-Price AG, McKenzie RM, Casiano CA, Fletcher HM (May 2008). "Gingipain-dependent interactions with the host are important for survival of Porphyromonas gingivalis". Frontiers in Bioscience. 13 (13): 3215–38. doi:10.2741/2922. PMC   3403687 . PMID   18508429.
  14. 1 2 Grenier D, Imbeault S, Plamondon P, Grenier G, Nakayama K, Mayrand D (August 2001). "Role of gingipains in growth of Porphyromonas gingivalis in the presence of human serum albumin". Infection and Immunity. 69 (8): 5166–72. doi:10.1128/IAI.69.8.5166-5172.2001. PMC   98614 . PMID   11447200.
  15. 1 2 3 4 5 Furuta N, Takeuchi H, Amano A (November 2009). "Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment". Infection and Immunity. 77 (11): 4761–70. doi:10.1128/IAI.00841-09. PMC   2772519 . PMID   19737899.
  16. ↑ Meuric V, Martin B, Guyodo H, Rouillon A, Tamanai-Shacoori Z, Barloy-Hubler F, et al. (February 2013). "Treponema denticola improves adhesive capacities of Porphyromonas gingivalis". Molecular Oral Microbiology. 28 (1): 40–53. doi:10.1111/omi.12004. PMID   23194417.
  17. 1 2 3 4 5 Kuboniwa M, Hasegawa Y, Mao S, Shizukuishi S, Amano A, Lamont RJ, et al. (February 2008). "P. gingivalis accelerates gingival epithelial cell progression through the cell cycle". Microbes and Infection. 10 (2): 122–8. doi:10.1016/j.micinf.2007.10.011. PMC   2311419 . PMID   18280195.
  18. ↑ McAlister AD, Sroka A, Fitzpatrick RE, Quinsey NS, Travis J, Potempa J, et al. (June 2009). "Gingipain enzymes from Porphyromonas gingivalis preferentially bind immobilized extracellular proteins: a mechanism favouring colonization?". Journal of Periodontal Research. 44 (3): 348–53. doi:10.1111/j.1600-0765.2008.01128.x. PMC   2718433 . PMID   18973544.
  19. 1 2 3 Vincents B, Guentsch A, Kostolowska D, von Pawel-Rammingen U, Eick S, Potempa J, et al. (October 2011). "Cleavage of IgG1 and IgG3 by gingipain K from Porphyromonas gingivalis may compromise host defense in progressive periodontitis". FASEB Journal. 25 (10): 3741–50. doi: 10.1096/fj.11-187799 . PMC   3177567 . PMID   21768393.
  20. 1 2 Grenier D, Tanabe S (March 2010). "Porphyromonas gingivalis gingipains trigger a proinflammatory response in human monocyte-derived macrophages through the p38α mitogen-activated protein kinase signal transduction pathway". Toxins. 2 (3): 341–52. doi: 10.3390/toxins2030341 . PMC   3153194 . PMID   22069588.
  21. ↑ Khalaf H, Bengtsson T (2012). Das G (ed.). "Altered T-cell responses by the periodontal pathogen Porphyromonas gingivalis". PLOS ONE. 7 (9): e45192. Bibcode:2012PLoSO...745192K. doi: 10.1371/journal.pone.0045192 . PMC   3440346 . PMID   22984628.
  22. 1 2 Singh A, Wyant T, Anaya-Bergman C, Aduse-Opoku J, Brunner J, Laine ML, et al. (November 2011). "The capsule of Porphyromonas gingivalis leads to a reduction in the host inflammatory response, evasion of phagocytosis, and increase in virulence". Infection and Immunity. 79 (11): 4533–42. doi:10.1128/IAI.05016-11. PMC   3257911 . PMID   21911459.
  23. ↑ d'Empaire G, Baer MT, Gibson FC (November 2006). "The K1 serotype capsular polysaccharide of Porphyromonas gingivalis elicits chemokine production from murine macrophages that facilitates cell migration". Infection and Immunity. 74 (11): 6236–43. doi:10.1128/IAI.00519-06. PMC   1695525 . PMID   16940143.
  24. ↑ Gonzalez D, Tzianabos AO, Genco CA, Gibson FC (April 2003). "Immunization with Porphyromonas gingivalis capsular polysaccharide prevents P. gingivalis-elicited oral bone loss in a murine model". Infection and Immunity. 71 (4): 2283–7. doi:10.1128/IAI.71.4.2283-2287.2003. PMC   152101 . PMID   12654858.
  25. ↑ Tsuda K, Amano A, Umebayashi K, Inaba H, Nakagawa I, Nakanishi Y, et al. (2005). "Molecular dissection of internalization of Porphyromonas gingivalis by cells using fluorescent beads coated with bacterial membrane vesicle". Cell Structure and Function. 30 (2): 81–91. doi: 10.1247/csf.30.81 . hdl: 2297/14728 . PMID   16428861.
  26. ↑ Hajishengallis G, Wang M, Harokopakis E, Triantafilou M, Triantafilou K (October 2006). "Porphyromonas gingivalis fimbriae proactively modulate beta2 integrin adhesive activity and promote binding to and internalization by macrophages". Infection and Immunity. 74 (10): 5658–66. doi:10.1128/IAI.00784-06. PMC   1594907 . PMID   16988241.
  27. 1 2 Lin X, Wu J, Xie H (October 2006). "Porphyromonas gingivalis minor fimbriae are required for cell-cell interactions". Infection and Immunity. 74 (10): 6011–5. doi:10.1128/IAI.00797-06. PMC   1594877 . PMID   16988281.
  28. 1 2 Park Y, Simionato MR, Sekiya K, Murakami Y, James D, Chen W, et al. (July 2005). "Short fimbriae of Porphyromonas gingivalis and their role in coadhesion with Streptococcus gordonii". Infection and Immunity. 73 (7): 3983–9. doi:10.1128/IAI.73.7.3983-3989.2005. PMC   1168573 . PMID   15972485.
  29. ↑ Love RM, McMillan MD, Park Y, Jenkinson HF (March 2000). "Coinvasion of dentinal tubules by Porphyromonas gingivalis and Streptococcus gordonii depends upon binding specificity of streptococcal antigen I/II adhesin". Infection and Immunity. 68 (3): 1359–65. doi:10.1128/IAI.68.3.1359-1365.2000. PMC   97289 . PMID   10678948.
  30. ↑ Pierce DL, Nishiyama S, Liang S, Wang M, Triantafilou M, Triantafilou K, et al. (August 2009). "Host adhesive activities and virulence of novel fimbrial proteins of Porphyromonas gingivalis". Infection and Immunity. 77 (8): 3294–301. doi:10.1128/IAI.00262-09. PMC   2715668 . PMID   19506009.
  31. 1 2 3 4 Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. (November 2011). "Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement". Cell Host & Microbe. 10 (5): 497–506. doi:10.1016/j.chom.2011.10.006. PMC   3221781 . PMID   22036469.
  32. ↑ Wang M, Liang S, Hosur KB, Domon H, Yoshimura F, Amano A, et al. (December 2009). "Differential virulence and innate immune interactions of Type I and II fimbrial genotypes of Porphyromonas gingivalis". Oral Microbiology and Immunology. 24 (6): 478–84. doi:10.1111/j.1399-302X.2009.00545.x. PMC   2883777 . PMID   19832800.
  33. ↑ Liang S, Krauss JL, Domon H, McIntosh ML, Hosur KB, Qu H, et al. (January 2011). "The C5a receptor impairs IL-12-dependent clearance of Porphyromonas gingivalis and is required for induction of periodontal bone loss". Journal of Immunology. 186 (2): 869–77. doi:10.4049/jimmunol.1003252. PMC   3075594 . PMID   21149611.
  34. ↑ Hajishengallis G, Wang M, Liang S, Triantafilou M, Triantafilou K (September 2008). "Pathogen induction of CXCR4/TLR2 cross-talk impairs host defense function". Proceedings of the National Academy of Sciences of the United States of America. 105 (36): 13532–7. Bibcode:2008PNAS..10513532H. doi: 10.1073/pnas.0803852105 . PMC   2533224 . PMID   18765807.
  35. ↑ Mao S, Park Y, Hasegawa Y, Tribble GD, James CE, Handfield M, et al. (August 2007). "Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis". Cellular Microbiology. 9 (8): 1997–2007. doi:10.1111/j.1462-5822.2007.00931.x. PMC   2886729 . PMID   17419719.
  36. ↑ Hajishengallis G (2009). "Porphyromonas gingivalis-host interactions: open war or intelligent guerilla tactics?". Microbes and Infection. 11 (6–7): 637–45. doi:10.1016/j.micinf.2009.03.009. PMC   2704251 . PMID   19348960.
  37. ↑ Darveau RP, Hajishengallis G, Curtis MA (September 2012). "Porphyromonas gingivalis as a potential community activist for disease". Journal of Dental Research. 91 (9): 816–20. doi:10.1177/0022034512453589. PMC   3420389 . PMID   22772362.
  38. ↑ Guyodo H, Meuric V, Le Pottier L, Martin B, Faili A, Pers JO, et al. (March 2012). "Colocalization of Porphyromonas gingivalis with CD4+ T cells in periodontal disease". FEMS Immunology and Medical Microbiology. 64 (2): 175–83. doi: 10.1111/j.1574-695x.2011.00877.x . PMID   22066676.
  39. ↑ Inagaki S, Onishi S, Kuramitsu HK, Sharma A (September 2006). "Porphyromonas gingivalis vesicles enhance attachment, and the leucine-rich repeat BspA protein is required for invasion of epithelial cells by "Tannerella forsythia"". Infection and Immunity. 74 (9): 5023–8. doi:10.1128/IAI.00062-06. PMC   1594857 . PMID   16926393.
  40. ↑ Verma RK, Rajapakse S, Meka A, Hamrick C, Pola S, Bhattacharyya I, et al. (2010). "Porphyromonas gingivalis and Treponema denticola Mixed Microbial Infection in a Rat Model of Periodontal Disease". Interdisciplinary Perspectives on Infectious Diseases. 2010: 605125. doi: 10.1155/2010/605125 . PMC   2879544 . PMID   20592756.
  41. ↑ Sanz M, Marco Del Castillo A, Jepsen S, Gonzalez-Juanatey JR, D'Aiuto F, Bouchard P, et al. (March 2020). "Periodontitis and cardiovascular diseases: Consensus report". Journal of Clinical Periodontology. 47 (3): 268–288. doi:10.1111/jcpe.13189. PMC   7027895 . PMID   32011025.
  42. ↑ Gibson FC, Hong C, Chou HH, Yumoto H, Chen J, Lien E, et al. (June 2004). "Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice". Circulation. 109 (22): 2801–2806. doi:10.1161/01.CIR.0000129769.17895.F0. PMID   15123526.
  43. ↑ Paul O, Arora P, Mayer M, Chatterjee S (2021-01-14). "Inflammation in Periodontal Disease: Possible Link to Vascular Disease". Frontiers in Physiology. 11: 609614. doi: 10.3389/fphys.2020.609614 . PMC   7841426 . PMID   33519515.
  44. ↑ Zhang J, Xie M, Huang X, Chen G, Yin Y, Lu X, et al. (2021-12-23). "The Effects of Porphyromonas gingivalis on Atherosclerosis-Related Cells". Frontiers in Immunology. 12: 766560. doi: 10.3389/fimmu.2021.766560 . PMC   8734595 . PMID   35003080.
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